One goal of this proposal is to study the alteration of the regulation of cellular DNA synthesis in SV40 transformed cells and to characterize the infected but non-transformed cells. We propose to isolate a polyphoid cell population(s) which is induced 24-48 hours post-infection and determine the relationship of these polyploid cells to transformation with SV40 virus. The system we propose to use is a contact inhibited Chinese hamster cell strain. We have previously shown this cell strain to be 1) diploid, 2) non-permissive to complete virus replication, 3) highly susceptible to SV40 infection (approximately 100 percent of the cells are infected), and 4) approximately 0.1-5 percent of the cells are transformed. The infected but non-transformed cells will be isolated, biologically characterized and studied in relation to their susceptibility to transformation by other carcinogenic agents. Another cell model which we have developed will be of interest in the study of the expression of the SV40 genome in differentiating cells. We have adapted the stem cell, embryonal carcinoma, of a spontaneous testicular teratocarcinoma to in vitro culture conditions. The embryonal carcinoma retains the potential to differentiate in vitro and in vivo. The embryonal carcinoma will be infected with SV40 virus to study the expression of the virus genome and its effect on differentiation of the tumor cells. If differentiation occurs, studies will be made to see if the process of differentiation can control the expression of viral DNA.